Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination

Schott, M.; Feldkamp, Joachim; Klucken, M; Kobbe, Guido; Scherbaum, Werner A.; Seißler, Jochen

doi:10.1007/s00262-002-0325-z

Cited by 46 publications

(30 citation statements)

References 17 publications

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“…Toxicity was acceptable, and one partial response was reported. Schott et al reported treatment of seven patients with MTC by immunotherapy with calcitonin-pulsed dendritic cells [47]. One significant response was seen in this preliminary study.…”

Section: Management Of Patients With Persistent or Recurrent Calcitonsupporting

confidence: 49%

Medullary thyroid carcinoma: Including MEN 2A and MEN 2B syndromes

Quayle

Moley

2005

Journal of Surgical Oncology

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Medullary thyroid carcinoma (MTC) is a rare malignancy with several distinctive features that distinguish its management from other thyroid cancers. First, MTC may be sporadic (75% of cases), or may occur as a manifestation of the hereditary syndrome Multiple Endocrine Neoplasia type 2 (MEN 2) (25% of cases). Additionally, while MTC is more difficult to cure than differentiated thyroid cancer and has higher rates of recurrence and mortality, it is usually a slow growing tumor compared with other malignancies. Finally, unlike differentiated thyroid cancer, there is no known effective systemic therapy for MTC. MTC cells do not concentrate radioactive iodine, and MTC does not respond well to external beam radiation or conventional cytotoxic chemotherapy. These distinguishing features should be considered in planning surgical management of MTC.

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Section: Management Of Patients With Persistent or Recurrent Calcitonsupporting

confidence: 49%

Medullary thyroid carcinoma: Including MEN 2A and MEN 2B syndromes

Quayle

Moley

2005

Journal of Surgical Oncology

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“…MTC belongs to the group of neuroendocrine cancers specifically characterized by the expression of calcitonin, 32-aa-long tumor-specific peptide. In the past, we already described that calcitonin may serve as specific tumor Ag useful for vaccination strategies in patients with MTC (21). Following IFN-DC treatment, we now report that two patients do not show any substantial changes in tumor morphology after long-term follow-up.…”

Section: Ifn-dcs As Well As Cd56mentioning

confidence: 57%

IFN-α Skews Monocytes into CD56+-Expressing Dendritic Cells with Potent Functional Activities In Vitro and In Vivo

Papewalis

Jacobs

Wuttke

et al. 2008

The Journal of Immunology

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105

101

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The antitumor effect of IFN-α is mediated by the activation of CTLs, NK cells, and the generation of highly potent Ag-presenting dendritic cells (IFN-DCs). In this study, we show that IFN-DCs generated in vitro from monocytes express CD56 on their surface, a marker which has been thought to be specific for NK cells. FACS analyses of CD56+ and CD56− IFN-DCs showed a nearly identical pattern for most of the classical DC markers. Importantly, however, only CD56+ IFN-DCs exhibited cytolytic activity up to 24% that could almost completely be blocked (−81%) after coincubation with anti-TRAIL. Intracytoplasmatic cytokine staining revealed that the majority of IFN-DCs independently of their CD56 expression were IFN-γ positive as well. In contrast, CD56+ IFN-DCs showed stronger capacity in stimulating allogenic T cells compared with CD56− IFN-DC. Based on these results, five patients with metastasized medullary thyroid carcinoma were treated for the first time with monocyte-derived tumor Ag-pulsed IFN-DCs. After a long term follow-up (in mean 37 mo) all patients are alive. Immunohistochemical analyses of delayed-type hypersensitivity skin reaction showed a strong infiltration with CD8+ cells. In two patients no substantial change in tumor morphology was detected. Importantly, by analyzing PBMCs, these patients also showed an increase of Ag-specific IFN-γ-secreting T cells. In summary, we here describe for the first time that cytotoxic activity of IFN-DCs is mainly mediated by an IFN-DC subset showing partial phenotypic and functional characteristics of NK cells. These cells represent another mechanism of the antitumor effect induced by IFN-α.

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“…In addition, three patients developed significant T-cell proliferation of peripheral blood lymphocytes in response to calcitonin and CEA. Peripheral blood lymphocytes drawn after initiation of treatment responded with high-level IFN-g secretion in some patients after stimulation with calcitonin or CEA, whereas the IL-4 production was only slightly increased Endocrine-Related Cancer (2006) 13 779-795 www.endocrinology-journals.org (Schott et al 2002). These data indicate the induction of a Th1-dominated cellular immune response against calcitonin and CEA in the majority of patients.…”

Section: Vaccination Trials In Mtcmentioning

confidence: 87%

Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers

Schott

2006

Endocr Relat Cancer

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Dendritic cells (DCs) are highly efficient antigen-presenting cells in the immune system with the potential to regulate the system and induce a cytotoxic T-cell response. As a proof of principle, a multitude of animal and human studies has demonstrated that immunization with antigen-loaded DCs may lead to anti-tumour immune responses with tumour regression and rejection of cancer. The identification of tumour antigens that can be recognized by T lymphocytes has facilitated the development of new protocols and enabled immunologists to monitor immune responses. However, to date, long-term clinical effects on larger numbers of cancer patients are missing, and there is no generally accepted DC generation or activation protocol. This review will focus on the most important findings on the role of DCs within the immune system and how to generate and activate these cells in order to induce cytotoxic immunity in non-endocrine and endocrine malignancies. Recently, we and other researchers reported on DC vaccinations in patients with endocrine malignancies mainly in metastasized medullary thyroid carcinoma resulting in tumourspecific immunity and partial clinical responses in some cases. Based on these and other in vitro data, new DC vaccination protocols for the treatment of patients with endocrine tumours have now been conducted.

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Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination

Cited by 46 publications

References 17 publications

Medullary thyroid carcinoma: Including MEN 2A and MEN 2B syndromes

Medullary thyroid carcinoma: Including MEN 2A and MEN 2B syndromes

IFN-α Skews Monocytes into CD56+-Expressing Dendritic Cells with Potent Functional Activities In Vitro and In Vivo

Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers

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